Safety and Efficacy of Donor T-lymphocytes Depleted ex Vivo of Host Alloreactive T-cells (ATIR) in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01794299
Recruitment Status : Completed
First Posted : February 18, 2013
Last Update Posted : November 17, 2017
Information provided by (Responsible Party):
Kiadis Pharma

Brief Summary:
The purpose of this study is to determine whether ATIR is safe and effective in reducing transplant-related mortality and improving overall survival, when infused in patients with a hematologic malignancy following a T-cell depleted stem cell graft from a related haploidentical donor.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndrome Biological: ATIR Phase 2

Detailed Description:
Study CR-AIR-007 is an exploratory, open-label, multicenter study. After signing informed consent, patients will receive a hematopoietic stem cell transplantation (HSCT) from a related, haploidentical donor, followed by infusion with ATIR between 28 and 32 days after the HSCT (or later if required by the patient's medical condition). Patients will receive ATIR as a single infusion at a dose of 2x10E6 viable T-cells/kg. All patients treated with ATIR will be followed up until 12 months after the HSCT. Assessments will be performed at weekly visits from the day of ATIR infusion until 8 weeks after ATIR infusion, at monthly visits from 3 until 6 months after the HSCT, every 2 months from 6 until 12 months after the HSCT, and every 6 months from 12 until 24 months after the HSCT.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of ATIR, Donor T-lymphocytes Depleted ex Vivo of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy, Who Received a CD34-selected Hematopoietic Stem Cell Transplantation From a Haploidentical Donor
Actual Study Start Date : March 2013
Actual Primary Completion Date : June 2016
Actual Study Completion Date : September 2017

Arm Intervention/treatment
Experimental: ATIR Biological: ATIR
Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.

Primary Outcome Measures :
  1. Transplant-related mortality (TRM) [ Time Frame: At 6 months post HSCT ]

Secondary Outcome Measures :
  1. Immune reconstitution [ Time Frame: Up to 24 months post HSCT ]
  2. TRM [ Time Frame: Up to 24 months post HSCT ]
  3. Relapse-related mortality (RRM) [ Time Frame: Up to 24 months post HSCT ]
  4. Overall survival (OS) [ Time Frame: Up to 24 months post HSCT ]
  5. Progression-free survival (PFS) [ Time Frame: Up to 24 months post HSCT ]
  6. Incidence of viral, fungal, and bacterial infections [ Time Frame: Up to 24 months post HSCT ]
  7. Severity of viral, fungal, and bacterial infections [ Time Frame: Up to 24 months post HSCT ]
  8. Incidence of acute and chronic graft versus host disease (GvHD) [ Time Frame: Up to 24 months post HSCT ]
  9. Severity of acute and chronic GvHD [ Time Frame: Up to 24 months post HSCT ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Any of the following hematologic malignancies: a) Acute myeloid leukemia (AML) in first remission with high-risk features or in second or higher remission b) Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or in second or higher remission c) Myelodysplastic syndrome (MDS): transfusion-dependent, or intermediate or higher Revised International Prognostic Scoring System (IPSS-R) risk group
  • Eligible for haploidentical stem cell transplantation according to the investigator

Exclusion Criteria:

  • Availability of a suitable matched related or unrelated donor following a donor search
  • In second or higher remission with the previous remission having lasted less than 6 months
  • Diffusing capacity for carbon monoxide (DLCO) < 50% predicted
  • Left ventricular ejection fraction < 50% (evaluated by echocardiogram or multiple gated acquisition [MUGA])
  • Aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN)(CTCAE grade 2)
  • Bilirubin > 1.5 x ULN (CTCAE grade 2)
  • Creatinine clearance < 50 mL/min (calculated or measured)
  • Positive test for human immunodeficiency virus (HIV)
  • Positive pregnancy test (women of childbearing age only)
  • Prior allogeneic stem cell transplantation using stem cells from a matched sibling donor, a matched unrelated donor, a haploidentical donor, or a cord blood donor
  • Prior autologous stem cell transplantation
  • Stay at intensive care unit for more than 2 months in the preceding 12 months
  • Estimated probability of surviving less than 3 months
  • Known allergy to any of the components of ATIR (e.g., dimethyl sulfoxide)
  • Any other condition which, in the opinion of the investigator, makes the patient ineligible for the study

Donor inclusion criteria

  • Haploidentical family donor with 2 to 3 mismatches at the HLA-A, -B and/or -DR loci of the unshared haplotype
  • Male or female, age ≥ 16 and ≤ 75 years
  • Eligible for donation according to the transplantation center

Donor exclusion criteria

  • Positive viral test for HIV-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, human T-lymphotropic virus (HTLV)-1*, HTLV-2*, or WNV* (if tested) (* at Canadian centers only)
  • Positive pregnancy test or nursing (women of childbearing age only)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01794299

Algemeen Ziekenhuis Sint-Jan
Brugge, Belgium, 8000
Université Libre de Bruxelles - Institute Jules Bordet
Brussels, Belgium, 1000
Universitair Ziekenhuis Gasthuisberg
Leuven, Belgium, 3000
Canada, Ontario
Juravinski Hospital and Cancer Centre
Hamilton, Ontario, Canada, L8V 1C3
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
Universitätsklinikum Würzburg
Würzburg, Germany, 97080
United Kingdom
Hammersmith Hospital
London, United Kingdom, W12 ONN
Sponsors and Collaborators
Kiadis Pharma
Study Chair: Denis Claude Roy, Prof MD Maisonneuve-Rosemont Hospital, Montreal Quebec

Responsible Party: Kiadis Pharma Identifier: NCT01794299     History of Changes
Other Study ID Numbers: CR-AIR-007
2012-004461-41 ( EudraCT Number )
File # 9427-K0980\1-21C ( Other Identifier: Health Canada )
First Posted: February 18, 2013    Key Record Dates
Last Update Posted: November 17, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Kiadis Pharma:
Haploidentical stem cell transplantation
Graft-versus-host disease
Immune reconstitution
Alloreactive T-cells
Photodynamic treatment
Transplant-related mortality
Hematologic malignancy

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases